Electrophoretic variants of blood proteins in Japanese VI. Transferrin

A multiplicity of transferrin variants have been detected in the course of the biochemical aspect of the study of the genetic effects of atomic bombs. Variants obtained from the studies of 19,770 individuals in Hiroshima and Nagasaki were compared by polyacrylamide slab gel electrophoresis using three kinds of buffer systems with different pH values and thin layer polyacrylamide gel isoelectric focusing. The variants were compared on the basis of their relative mobilities and isoelectric points; seven types of fast-moving variant (B-variant) and nine types of slow-moving variant (D-variant) were detected, involving a total of 154 and 273 individuals, respectively. All the variants were identified as genetic variants by family studies. No variant differend inaallele frequency between the two cities. The variants detected in this study were compared with variants detected in residents of Mie district (another Japanese population), Caucasoids, American blacks, and Amerindians. Six additional types of B-variant and four additional types of D-variant, which had not been detected in Hiroshima and Nagasaki, were identified.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41593/1/10038_2005_Article_BF01876469.pd

A Critical Role of Fatty Acid Binding Protein 4 and 5 (FABP4/5) in the Systemic Response to Fasting

During prolonged fasting, fatty acid (FA) released from adipose tissue is a major energy source for peripheral tissues, including the heart, skeletal muscle and liver. We recently showed that FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipocytes and macrophages, are prominently expressed in capillary endothelial cells in the heart and skeletal muscle. In addition, mice deficient for both FABP4 and FABP5 (FABP4/5 DKO mice) exhibited defective uptake of FA with compensatory up-regulation of glucose consumption in these tissues during fasting. Here we showed that deletion of FABP4/5 resulted in a marked perturbation of metabolism in response to prolonged fasting, including hyperketotic hypoglycemia and hepatic steatosis. Blood glucose levels were reduced, whereas the levels of non-esterified FA (NEFA) and ketone bodies were markedly increased during fasting. In addition, the uptake of the 125I-BMIPP FA analogue in the DKO livers was markedly increased after fasting. Consistent with an increased influx of NEFA into the liver, DKO mice showed marked hepatic steatosis after a 48-hr fast. Although gluconeogenesis was observed shortly after fasting, the substrates for gluconeogenesis were reduced during prolonged fasting, resulting in insufficient gluconeogenesis and enhanced hypoglycemia. These metabolic responses to prolonged fasting in DKO mice were readily reversed by re-feeding. Taken together, these data strongly suggested that a maladaptive response to fasting in DKO mice occurred as a result of an increased influx of NEFA into the liver and pronounced hypoglycemia. Together with our previous study, the metabolic consequence found in the present study is likely to be attributed to an impairment of FA uptake in the heart and skeletal muscle. Thus, our data provided evidence that peripheral uptake of FA via capillary endothelial FABP4/5 is crucial for systemic metabolism and may establish FABP4/5 as potentially novel targets for the modulation of energy homeostasis

Carbonyl Sulfide Hydrolase from <i>Thiobacillus thioparus</i> Strain THI115 Is One of the β‑Carbonic Anhydrase Family Enzymes

Carbonyl sulfide (COS) is an atmospheric trace gas leading to sulfate aerosol formation, thereby participating in the global radiation balance and ozone chemistry, but its biological sinks are not well understood. <i>Thiobacillus thioparus</i> strain THI115 can grow on thiocyanate (SCN^–) as its sole energy source. Previously, we showed that SCN^– is first converted to COS by thiocyanate hydrolase in <i>T. thioparus</i> strain THI115. In the present work, we purified, characterized, and determined the crystal structure of carbonyl sulfide hydrolase (COSase), which is responsible for the degradation of COS to H₂S and CO₂, the second step of SCN^– assimilation. COSase is a homotetramer composed of a 23.4 kDa subunit containing a zinc ion in its catalytic site. The amino acid sequence of COSase is homologous to the β-class carbonic anhydrases (β-CAs). Although the crystal structure including the catalytic site resembles those of the β-CAs, CO₂ hydration activity of COSase is negligible compared to those of the β-CAs. The α5 helix and the extra loop (Gly150–Pro158) near the N-terminus of the α6 helix narrow the substrate pathway, which could be responsible for the substrate specificity. The <i>k</i>_cat/<i>K</i>_m value, 9.6 × 10⁵ s^–1 M^–1, is comparable to those of the β-CAs. COSase hydrolyzes COS over a wide concentration range, including the ambient level, <i>in vitro</i> and <i>in vivo</i>. COSase and its structurally related enzymes are distributed in the clade D in the phylogenetic tree of β-CAs, suggesting that COSase and its related enzymes are one of the catalysts responsible for the global sink of COS